1. Field of the invention:
This invention embodies a new and novel process for the preparation of analgesics and/or narcotic antagonists.
2. Description of the prior art:
A. (-)-14-hydroxy-3-methoxy-N-methylmorphinan and derivatives thereof have been described by Y. K. Sawa and H. Tada in Tetrahedron, 24, pp. 6185-6196. This paper reports the compound 14-hydroxy-3-methoxy-N-methylmorphinan as being prepared from 14-hydroxydehydrothebainone, an opium alkaloid.
B. U.S. Pat. No. 3,166,599 disclosed compounds having the generic formula ##SPC2##
And ##SPC3##
In which R represents a hydrogen atom or a (lower)-alkyl group (e.g., methyl, ethyl, propyl), R.sup.1 represents a hydrogen atom, an aryloxy group (e.g., phenyloxy, naphthyloxy) or a substituted phenyloxy, substituted naphthyloxy wherein the substituent is (lower)alkyl (e.g., methyl, ethyl, propyl), (lower)alkoxy, (e.g., methoxy, ethoxy, propoxy), nitro or amino, X represents a hydrogen atom or a hydroxyl group and, in Formula I, one or two double bond(s) exist(s) in the C ring.
C. British Pat. No. 1,028,407 discloses compounds having the generic formula ##SPC4##
Wherein R represents an alkyl group having not more than five carbon atoms (e.g., methyl, ethyl, propyl), R.sup.1 represents a hydrogen atom or an aryloxy group (e.g., phenyloxy or naphthyloxy), R" represents a methylene group, a carbonyl group or a ketalated carbonyl group (e.g., ethylenedioxymethylene or diethoxymethylene), X represents a hydrogen atom or hydroxyl group and Y represents an alkyl group having not more than five carbon atoms (e.g., methyl, ethyl or propyl), an aryl group (e.g., phenyl or naphthyl) or an aralkyl group in which the alkyl moiety has not more than five carbon atoms (e.g., benzyl or phenethyl) and shows various pharmacological activities such as analgesic activity, antitussive activity and anti-inflammatory activity.
D. U.S. Pat. No. 3,775,414 discloses or claims a process for the preparation of the identical compounds to which this patent application is directed. Claim 1 of that patent is as follows:
The process for the preparation of compounds having the formula ##SPC5##
In which R.sup.3 is (lower)alkyl, which process comprises the consecutive steps of
A. brominating the compound having the formula ##SPC6##
In which R.sup.3 is (lower)alkyl, with liquid bromine in chloroform, carbon tetrachloride, benzene, toluene, xylene or methylene chloride in a ratio of about 1 mole of bromine per mole of compound Va, at about -15.degree.C. to about +45.degree.C., with stirring to produce the compound having the formula ##SPC7##
in which R.sup.3 is (lower)alkyl; and
B. heating Compound VIa in the presence of anhydrous sodium or potassium bicarbonate in dimethylformamide, benzene, dimethylacetamide, toluene, xylene, dioxane or tetrahydrofuran, in a ratio of no more than 1 mole of bicarbonate per mole of Compound VIa to produce Compound XIa.
E. U.S. Pat. No. 3,819,635 discloses and claims the compounds having the formula ##SPC8##
wherein R.sup.1 is selected from the group comprising ##EQU1## ##SPC9## and (lower)alkenyl in which R.sup.4 is H or CH.sub.3, R.sup.2 is selected from the group comprising H, (lower)alkyl, ##SPC10##
R is H, (lower)acyl, trichloroacetyl or cinnamoyl; or a pharmaceutically acceptable acid addition salt thereof and a process for their preparation which differs from that taught in reference E supra and that claimed in this invention.